Pediatric Type 1 Diabetes Mellitus Guidelines

ADA: Position statement on type 1 diabetes in children and adolescents

In August 2018, the American Diabetes Association released a position statement on type 1 diabetes in children and adolescents, which included the following guidelines ^{[70, 71]} :

• Consult a pediatric endocrinologist before diagnosing type 1 diabetes when isolated glycosuria or hyperglycemia is discovered in patients with acute illness in the absence of classic symptoms
• Differentiating type 1 diabetes, type 2 diabetes, monogenic diabetes, and other forms of diabetes is based on patient history and characteristics, as well as on laboratory tests, such as an islet autoantibody panel
• The majority of children with type 1 diabetes should be treated with intensive insulin regimens using multiple daily injections of prandial insulin and basal insulin or continuous subcutaneous insulin infusion
• A _1C should be measured every 3 months
• Blood glucose levels should be monitored up to 6-10 times daily
• Continuous glucose monitors (CGM) should be considered in all children and adolescents with type 1 diabetes; the benefits of CGM correlate with adherence to ongoing use of the device
• Blood or urine ketone levels should be monitored in children with type 1 diabetes in the presence of prolonged/severe hyperglycemia or acute illness
• Individualized medical nutrition therapy is recommended for children and adolescents
• Exercise is recommended, with a goal of 60 minutes a day of moderate to vigorous aerobic activity, along with vigorous muscle-strengthening and bone-strengthening activities at least 3 days a week
• It is important to frequently monitor glucose before, during, and after exercise (with or without CGM use) to prevent, detect, and treat hypoglycemia and hyperglycemia
• All individuals with type 1 diabetes should have access to an uninterrupted supply of insulin; lack of access and insulin omissions are major causes of diabetic ketoacidosis
• Glucagon should be prescribed for all individuals with type 1 diabetes, and caregivers or family members should be instructed regarding administration
• Once the child has had diabetes for 5 years, annual screening for albuminuria, using a random spot urine sample (morning sample preferred to avoid effects of exercise) to assess the albumin-to-creatinine ratio, should be considered at puberty or at age greater than 10 years, whichever occurs earlier
• Once the youth has had diabetes for 3-5 years, an initial dilated and comprehensive eye examination is recommended at age 10 years or after puberty has started, whichever is earlier, and an annual routine follow-up is generally recommended
• For adolescents who have had type 1 diabetes for 5 years, consider an annual comprehensive foot exam at the start of puberty or at age 10 years, whichever is earlier
• Blood pressure should be measured at each routine visit; children who have high-normal blood pressure (systolic blood pressure [SBP] or diastolic blood pressure [DBP] at 90th percentile for age, sex, and height) or hypertension (SBP or DBP at 95th percentile for age, sex, and height) should have blood pressure confirmed on 3 separate days
• Initial treatment of high-normal blood pressure (SBP or DBP consistently at the 90th percentile for age, sex, and height) includes dietary modification and increased exercise for weight control; if target blood pressure is not reached within 3-6 months after lifestyle intervention, consider pharmacologic treatment
• Because of their potential teratogenic effects, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) should be considered for initial pharmacologic treatment of hypertension after reproductive counseling
• The blood pressure treatment goal is consistently less than the 90th percentile for age, sex, and height
• If low-density lipoprotein (LDL) cholesterol is within an acceptable risk level (< 100 mg/dL [2.6 mmol/L]), a lipid profile every 3-5 years is reasonable
• If lipid levels are abnormal, initial therapy should consist of optimizing glucose control and initiating a Step 2 American Heart Association diet (restricting saturated fat to 7% of total calories and dietary cholesterol to 200 mg/day)
• After age 10 years, consider adding a statin if, despite 6 months of medical nutrition therapy and lifestyle changes, LDL cholesterol remains greater than 160 mg/dL (4.1 mmol/L) or LDL cholesterol remains greater than 130 mg/dL (3.4 mmol/L) with one or more cardiovascular disease (CVD) risk factors present (after reproductive counseling because of the potential teratogenic effects of statins)
• The LDL therapy goal is less than 100 mg/dL (2.6 mmol/L)
• In children with type 1 diabetes, consider testing for antithyroid peroxidase and antithyroglobulin antibodies soon after diagnosis
• In children and adolescents with type 1 diabetes, an A _1C target of less than 7.5% should be considered but individualized
• Glucose (15 g) is preferred treatment for conscious individuals with hypoglycemia (blood glucose < 70 mg/dL [3.9 mmol/L]), but any form of carbohydrate may be used; treatment should be repeated if self-monitoring blood glucose (SMBG) 15 minutes after treatment shows hypoglycemia is still present; when blood glucose concentration returns to normal, consider a meal or snack and/or reduce insulin to prevent recurrence of hypoglycemia
• In patients with classic symptoms, blood glucose measurement is sufficient to diagnose diabetes (symptoms of hyperglycemia or hyperglycemic crisis and random plasma glucose ≥200 mg/dL [11.1 mmol/L])
• Measure thyroid-stimulating hormone concentrations when the patient is clinically stable or once glycemic control has been established; if normal, suggest rechecking every 1-2 years (or sooner if the patient develops symptoms or signs that suggest thyroid dysfunction, thyromegaly, an abnormal growth rate, or unexplained glycemic variability)
• Screen children for celiac disease by measuring IgA tissue transglutaminase antibodies
• Criteria for diagnosis of diabetes is fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L)
• In asymptomatic children and adolescents at high risk for diabetes, if FPG ≥126 mg/dL (7 mmol/L), if 2-hr PG ≥200 mg/dL (11.1 mmol/L), or if A _1C ≥6.5%, testing should be repeated on a separate day to confirm the diagnosis

ADA: Standards of Medical Care in Diabetes

The American Diabetes Association’s Standards of Medical Care in Diabetes-2018 include the following recommendations with regard to children and adolescents with type 1 diabetes ^[63] :

• At diagnosis and routinely thereafter, youth with type 1 diabetes and parents/caregivers (for patients aged < 18 years) should receive culturally sensitive and developmentally appropriate individualized diabetes self-management education and support according to national standards
• Encourage developmentally appropriate family involvement in diabetes management tasks for children and adolescents, recognizing that premature transfer of diabetes care to the child can result in nonadherence and deterioration in glycemic control
• Providers should consider asking youth and their parents about social adjustment (peer relationships) and school performance to determine whether further intervention is needed
• Assess youth with diabetes for psychosocial and diabetes-related distress, generally starting at age 7-8 years
• Starting at puberty, preconception counseling should be incorporated into routine diabetes care for all girls of childbearing potential
• The majority of children and adolescents with type 1 diabetes should be treated with intensive insulin regimens, either via multiple daily injections or continuous subcutaneous insulin infusion
• All children and adolescents with type 1 diabetes should self-monitor blood glucose levels multiple times daily, including premeal and prebedtime; as needed for safety in specific clinical situations, such as exercise or driving; and for symptoms of hypoglycemia
• Continuous glucose monitoring should be considered in children and adolescents with type 1 diabetes, whether they are using injections or continuous subcutaneous insulin infusion, as an additional tool to help improve glycemic control; benefits of continuous glucose monitoring correlate with adherence to ongoing use of the device
• Automated insulin delivery systems improve glycemic control and reduce hypoglycemia in adolescents and should be considered in adolescents with type 1 diabetes
• Assess for the presence of autoimmune conditions associated with type 1 diabetes soon after the diabetes diagnosis and if autoimmune disease symptoms develop
• Measure thyroid-stimulating hormone concentrations at diagnosis when clinically stable or soon after glycemic control has been established; if normal, consider rechecking every 1-2 years (or sooner if the patient develops symptoms suggestive of thyroid dysfunction, thyromegaly, an abnormal growth rate, or an unexplained glycemic variation)
• Screen individuals with type 1 diabetes for celiac disease soon after the diagnosis of diabetes by measuring immunoglobulin A (IgA) tissue transglutaminase antibodies, with documentation of normal total serum IgA levels or, if the patient is IgA deficient, IgG tissue transglutamine and deamidated gliadin antibodies
• Repeat screening for celiac disease within 2 years of diabetes diagnosis and then again after 5 years and consider more frequent screening in children who have symptoms or a first-degree relative with celiac disease
• Individuals with biopsy-confirmed celiac disease should be placed on a gluten-free diet and have a consultation with a dietitian experienced in managing diabetes and celiac disease
• Blood pressure should be measured at each routine visit; children found to have high-normal blood pressure (systolic blood pressure or diastolic blood pressure in the 90th percentile or above for age, sex, and height) or hypertension (systolic blood pressure or diastolic blood pressure in the 95th percentile or above for age, sex, and height) should have elevated blood pressure confirmed on 3 separate days
• Initial therapy for dyslipidemia should consist of optimizing glucose control and the employment of medical nutrition therapy (using a Step 2 American Heart Association diet) to decrease the amount of saturated fat in the diet
• After the age of 10 years, addition of a statin is suggested in patients who, despite medical nutrition therapy and lifestyle changes, continue to have a low-density lipoprotein (LDL) cholesterol level above 160 mg/dL (4.1 mmol/L) or an LDL cholesterol above 130 mg/dL (3.4 mmol/L) and one or more cardiovascular disease risk factors; however, statin use should follow reproductive counseling and implementation of effective birth control, due to the potential teratogenic effects of statins
• Elicit a smoking history at initial and follow-up diabetes visits; discourage smoking in youth who do not smoke, and encourage smoking cessation in those who do smoke
• Annual screening for albuminuria with a random spot urine sample for albumin-to-creatinine ratio should be performed at puberty or at age 10 years or older, whichever is earlier, once the child has had diabetes for 5 years
• When a persistently elevated urinary albumin-to-creatinine ratio (>30 mg/g) is documented with at least two of three urine samples, treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker may be considered and the dose titrated to maintain blood pressure within the age-appropriate normal range; the urine samples should be obtained over a 6-month interval following efforts to improve glycemic control and normalize blood pressure
• An initial dilated and comprehensive eye examination is recommended once a youth has had type 1 diabetes for 3-5 years, provided that he/she is age 10 years or older or puberty has started, whichever is earlier
• Consider an annual comprehensive foot exam at the start of puberty or at age 10 years or older, whichever is earlier, once the youth has had type 1 diabetes for 5 years

ISPAD: Diabetic vascular complications in children and adolescents

In August 2018, the International Society for Pediatric and Adolescent Diabetes (ISPAD) released clinical practice consensus guidelines on diabetic microvascular and macrovascular complications in children and adolescents. These include the following ^[72] :

• Commence screening for microvascular complications at age 11 years
• Screening for microvascular disease should be performed preconception and during each trimester of pregnancy
• Intensive education and treatment should be provided to children and adolescents to prevent or delay the onset and progression of vascular complications
• Achievement of target glycemic control will reduce the risk for onset and progression of diabetic vascular complications
• Prevention or cessation of smoking will reduce progression of albuminuria and cardiovascular disease
• Screening for diabetic retinopathy should start at age 11 years with 2 to 5 years’ diabetes duration
• Screening for diabetic retinopathy should be performed by an ophthalmologist or optometrist or a trained, experienced observer, through dilated pupils, with assessment carried out via biomicroscopic examination or fundal photography
• Laser treatment and intravitreal injections of anti–vascular endothelial growth factor (VEGF) agents reduce the rate of vision loss for individuals in vision-threatening stages of retinopathy (severe nonproliferative retinopathy or worse and/or diabetic macular edema)
• Screen for renal disease using first morning albumin/creatinine ratio as the preferred method.
• Blood pressure (BP) should be measured at least annually; hypertension is defined as average systolic BP (SBP) and/or diastolic BP (DBP) that is at or above the 95th percentile for gender, age, and height on three or more occasions
• Angiotensin-converting enzyme (ACE) inhibitors are recommended for use in children with diabetes and hypertension; they have been effective and safe in children in short-term studies but are not safe during pregnancy
• Screen for lipid abnormalities in the nonfasting state
• With regard to macrovascular disease, screening of BP and lipids is recommended, as above; the benefit of routine screening for other markers of macrovascular complications outside the research setting is unclear

ISPAD: Glycemic control targets and glucose monitoring in children, adolescents, and young adults

In July 2018, the ISPAD released clinical practice consensus guidelines on glycemic control targets and glucose monitoring in children, adolescents, and young adults with diabetes. These include the following ^[73] :

• Glycemic control of children and adolescents must be assessed by both quarterly hemoglobin A1c (HbA1c) measurements and by regular home glucose monitoring; these permit achievement of optimal health in the following ways: (1) by determining with accuracy and precision an individual's glycemic control, including through assessment of each individual's glycemic determinants; (2) by reducing the risks of acute and chronic disease complications; and (3) by minimizing the effects of hypoglycemia and hyperglycemia on brain development, cognitive function, and mood
• Regular self-monitoring of glucose (using accurate finger-stick blood glucose [BG] measurements, with or without continuous glucose monitoring [CGM] or intermittently scanned CGM [isCGM]), is essential for diabetes management for all children and adolescents with diabetes
• Each child should have access to technology and materials for self-monitoring of glucose measurements to provide for enough testing for optimized diabetes care
• When finger-stick BG measurements are used, testing may need to be performed 6-10 times per day to optimize intensive control; regular review of these BG values should be performed with adjustments to medication/nutritional therapies to optimize control
• Real-time CGM data particularly benefit children who cannot articulate symptoms of hypoglycemia or hyperglycemia and those with hypoglycemic unawareness
• Intermittently scanned CGM can complement finger-stick BG assessments. Although isCGM provides some benefits similar to those of CGM, it does not alert users to hypoglycemia or hyperglycemia in real time, nor does it permit calibration. Without robust pediatric use efficacy data, it cannot fully replace BG monitoring
• For children, adolescents, and young adults aged 25 years or younger, ISPAD recommends individualized targets, aiming for the lowest achievable HbA1c without undue exposure to severe hypoglycemia, balanced with quality of life and burden of care
• For children, adolescents, and young adults aged 25 years or younger who have access to comprehensive care, a target HbA1c of less than 53 mmol/mol (7.0%) is recommended
• A higher HbA1c goal (in most cases below 58 mmol/mol [7.5%]) is appropriate in the following contexts: (1) inability to articulate symptoms of hypoglycemia; (2) hypoglycemia unawareness/history of severe hypoglycemia; (3) lack of access to analog insulins, advanced insulin delivery technology, and CGM, and lack of ability to regularly check BG; and (4) individuals who are “high glycators,” in whom an at-target HbA1c would reflect a significantly lower mean glucose level than 8.6 mmoL/L (155 mg/dL)
• A lower goal (6.5%) or 47.5 mmol/mol may be appropriate if achievable without excessive hypoglycemia, impairment of quality of life, and undue burden of care
• A lower goal may be appropriate during the honeymoon phase of type 1 diabetes
• For patients who have elevated HbA1c, a stepwise approach to improve glycemic control is advised, including individualized attention to the following: (1) dose adjustments, (2) personal factors limiting achievement of the target, (3) assessment of the psychological effect of goal setting on the individual, and (4) incorporation of available technology to improve glucose monitoring and insulin delivery modalities
• HbA1c measurement should be available in all centers caring for persons with diabetes
• HbA1c measurements should be performed at least every 3 months
• Examining variations in HbA1c between centers can assist in evaluating the care provided by health-care centers, including compliance with agreed-to standards to improve therapies and delivery of pediatric diabetes care